Both RIG-I and MDA5 detect alphavirus replication in concentration-dependent mode

Abstract Alphaviruses are a family of positive-strand RNA viruses that circulate on all continents between mosquito vectors and vertebrate hosts. Despite a significant public health threat, their biology is not sufficiently investigated, and the mechanisms of alphavirus replication and virus–host in...

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Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2016-01, Vol.487, p.230-241
Main Authors: Akhrymuk, Ivan, Frolov, Ilya, Frolova, Elena I
Format: Article
Language:English
Subjects:
3T3 Cells
60 APPLIED LIFE SCIENCES
Alphavirus - genetics
Alphavirus - growth & development
Alphavirus - immunology
Alphaviruses
Animals
Cell Line
CONCENTRATION RATIO
Cricetinae
DEAD Box Protein 58
DEAD-box RNA Helicases - genetics
DEAD-box RNA Helicases - metabolism
DISEASE VECTORS
Gene Knock-In Techniques
Gene Knockdown Techniques
IMMUNITY
Immunity, Innate - immunology
IN VITRO
IN VIVO
Infectious Disease
Innate immunity
INTERFERON
Interferon-beta - immunology
Interferon-Induced Helicase, IFIH1
MDA5
Mice
MOSQUITOES
PATTERN RECOGNITION
Pattern recognition receptors
PUBLIC HEALTH
RECEPTORS
Receptors, Pattern Recognition - immunology
RIG-I
RNA
Type I interferon
VERTEBRATES
Virus Replication
VIRUSES
Virus–host interactions
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Summary:Abstract Alphaviruses are a family of positive-strand RNA viruses that circulate on all continents between mosquito vectors and vertebrate hosts. Despite a significant public health threat, their biology is not sufficiently investigated, and the mechanisms of alphavirus replication and virus–host interaction are insufficiently understood. In this study, we have applied a variety of experimental systems to further understand the mechanism by which infected cells detect replicating alphaviruses. Our new data strongly suggest that activation of the antiviral response by alphavirus-infected cells is determined by the integrity of viral genes encoding proteins with nuclear functions, and by the presence of two cellular pattern recognition receptors (PRRs), RIG-I and MDA5. No type I IFN response is induced in their absence. The presence of either of these PRRs is sufficient for detecting virus replication. However, type I IFN activation in response to pathogenic alphaviruses depends on the basal levels of RIG-I or MDA5.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2015.09.023